From its beginnings as a center which focused on behavioral, neuropsychological and neuropsychiatric changes over the course of the disease, the University of Pittsburgh Alzheimer's Disease Research Center (ADRC) has evolved into a broadly based, full-service dementia research center, fulfilling its missions in excellent patient care and follow-up, clinical, basic, and translational research, and education of students, residents, fellows, faculty, community physicians, and the lay community. Our areas of research specialization include neuropsychiatric symptoms and manifestations of Alzheimer's disease and other dementias, neuropathology, neuroimaging and new neuroimaging modalities, genetics, and overlap of Alzheimer's disease with other neurodegenerative disorders. A wide range of basic and clinical research studies are supported by patients, data, or biological materials from the ADRC. In this current renewal, the Center will support 6 cores, 3 research projects, and 2 pilot studies. One project will explore the compensatory mechanisms (and their failure) during the initial year after the diagnosis of Alzheimer's disease, a second will continue from the previous grant period to assess the natural history of amyloid deposition in the brains of patients with autosomal dominant familial Alzheimer's disease and the third will examine alterations in microglial structure and function in aging and Alzheimer's disease. The Pitt ADRC has also provided national and international leadership to the Centers program and other collaborative efforts in Alzheimer's disease, in the ADC directors group, the ADC administrators group, the AD Cooperative Study, and the NACC. Members of the Pittsburgh ADRC sit on advisory committees for a variety of other Alzheimer's centers as well as the national Alzheimer's Association and have been awarded some of the most prestigious research awards in the field of Alzheimer's disease research for their contributions. PUBLIC HEALTH RELEVANCE: Beyond the statistic that more than 5 million people currently have Alzheimer's disease and the fact that this number will mushroom as baby-boomers pass through the age of risk is the simple reality that Alzheimer's disease is feared second only to cancer when Americans consider their long-term health prospects. Alzheimer's centers such as the one in Pittsburgh play a critical role in the nation's struggle to: 1) care for those currently afflicted; 2) improve diagnosis and treatment; and 3) find a means of prevention.